1. Field of the Invention
The present invention is generally related to structures of asymmetric compounds, and more particularly to structures of camphor-derived chiral auxiliary and the method for forming the same.
2. Description of the Prior Art
A survey by Frost & Sullivan estimates that global sales of single-enantiomer compounds are expected to reach $8.57 billion by the end of 2004, $9.5 billion by 2005, and $14.94 billion by 2009, growing annually by 11.4%. Furthermore, chiral industry could be divided into two groups: manufacturing of chiral compounds and analysis of chiral compounds, wherein manufacturing of chiral compounds dominate most of the market, and manufacturing of chiral compounds could be further divided into chiral synthesis and chiral separation. Comparing to chiral separation, the marker size of chiral synthesis is much bigger. Additionally, according to the selling report (from “CHIRAL CHEMISTRY”, Chemical & Engineering Story, Jun. 14, 2004, Volume 82, Number 24, pp. 47-62), in nine of top 10 drugs, the active ingredients are chiral. Therefore, chiral compound plays an important role in pharmacy.
A variety of reactions can be catalyzed by specially-designed chiral auxiliaries, wherein many products, such as drug intermediates, are fabricated with high diastereoselectivity. A well known example is that American company Monsanto employed a forming method, developed by Knowles, W. S., to produce a drug treatment for Parkinson's Disease (PD), and this drug is L-DOPA [(3,4-dihydroxyphenyl)-L-alanine]. Patients with PD are lack of dopamine (DA) in basal ganglia in their brain. Moreover, in the animal and human body L-DOPA was enzymatically converted to DA, and that's why L-DOPA is chosen to be the treatment for PD. In the research field based on Knowles, after more than thirty years' development, chemists have successfully prepared hundreds and hundreds chiral auxiliaries and catalysts, which are applied in many organic reactions. Therefore, optically active products from those organic reactions are obtained in relative high enantiomeric purity.

It is another example demonstrated that Oppolzer's camphor sultam serves as an effective chiral auxiliary for optically active products. The group of Bernard P. ROQUES in 1995 has already reported that 4-phosphonomethyl-phenylalanine (Pmp) was successfully prepared by using derivatives of Oppolzer's camphor sultam. Phosphorylation and dephosphorylation reactions on tyrosine residues of proteins play important roles in cellular signal transduction. These processes are mediated by proteins endowed with tyrosine kinase (PTK) and phosphatase (PTP) enzymatic activities. The aberrant expression of PTK and PTP can lead to neoplastic cell transformation. It is therefore of great interest to develop inhibitors of these recognition process in order to study the signaling pathways and to search for potential antitumor agents. This could be done by using small peptides derived from the enzyme sequence surrounding the O-phosphotyrosine residue, and the stable analoge 4-phosphonomethyl-phenylalanine (Pmp) was proposed as an hydrolytically stable analogue of O-phosphotyrosine. As shown in the following scheme, good stereocontrol of Pmp has been achieved by using derivatives of Oppolzer's camphor sultam as chiral auxiliary.

In summary, chiral auxiliaries hold considerable potential for the asymmetric synthesis. At present, most commercial chiral auxiliaries face some problems that decelerate the growth rate of the market, such as high cost and complicated forming method. On the other hand, if recovery amount of used chiral auxiliary can be raised significantly, the operational cost will be reduced efficiently. In addition, as environmental issues have become highly regarded nowadays, new and appreciate structures of camphor-derived chiral auxiliary and the method for forming the same, is no doubt the trend in the future.